Effects of testosterone replacement in androgen-deficient women with hypopituitarism: a randomized, double-blind, placebo-controlled study.

CONTEXT Hypopituitarism in women is characterized by profound androgen deficiency due to a loss of adrenal and/or ovarian function. The effects of testosterone replacement in this population have not been reported. OBJECTIVE The objective of the study was to determine whether physiologic testosterone replacement improves bone density, body composition, and/or neurobehavioral function in women with severe androgen deficiency secondary to hypopituitarism. DESIGN This was a 12-month randomized, placebo-controlled study. SETTING The study was conducted at a general clinical research center. STUDY PARTICIPANTS Fifty-one women of reproductive age with androgen deficiency due to hypopituitarism participated. INTERVENTION Physiologic testosterone administration using a patch that delivers 300 microg daily or placebo was administered. MAIN OUTCOME MEASURES Bone density, fat-free mass, and fat mass were measured by dual x-ray absorptiometry. Thigh muscle and abdominal cross-sectional area were measured by computed tomography scan. Mood, sexual function, quality of life, and cognitive function were assessed using self-administered questionnaires. RESULTS Mean free testosterone increased into the normal range during testosterone administration. Mean hip (P = 0.023) and radius (P = 0.007), but not posteroanterior spine, bone mineral density increased in the group receiving testosterone, compared with placebo, as did mean fat-free mass (P = 0.040) and thigh muscle area (P = 0.038), but there was no change in fat mass. Mood (P = 0.029) and sexual function (P = 0.044) improved, as did some aspects of quality of life, but not cognitive function. Testosterone at physiologic replacement levels was well tolerated, with few side effects. CONCLUSIONS This is the first randomized, double-blind, placebo-controlled study to show a positive effect of testosterone on bone density, body composition, and neurobehavioral function in women with severe androgen deficiency due to hypopituitarism.